The Cellular Prion Protein Controls Notch Signalling in Neural Stem/Progenitor Cells
Séverine Martin-Lannerée, Sophie Halliez, Théo Z. Hirsch, Julia Hernandez-Rapp, Bruno Passet, Céline Tomkiewicz, Ana Villa-Diaz, Juan-Maria Torres, Jean-Marie Launay, Vincent Béringue, Jean-Luc Vilotte and Sophie Mouillet-Richard
Accepted manuscript online: 19 SEP 2016 03:48AM EST | DOI: 10.1002/stem.2501
Legend to graphical abstract
Model for PrPC action on Notch and stemness in neural progenitors:
PrPC positively regulates the expression of Notch ligands and that of the Notch receptors and its ablation compromises Notch signalling;
Proper Notch signalling supports N-cadherin-mediated cell-cell contacts as well as the expression of NSC markers and exerts a positive feedback action on PrPC;
Downstream from PrPC, Notch signalling additionally upregulates the expression of EGFR, which, when activated, negatively regulates both PrPC and Notch.
Thus, PrPC, the Notch pathway and EGFR belong to a gene regulatory network, whose imbalance may shift towards “more stemness” (higher Notch activity induces higher PrPC expression and vice-versa) or “less stemness” (EGFR activation dampens Notch signalling and PrPC expression).